Schedule H

Oral

Gemfibrozil capsules: 300 mg

Gemfibrozil tablets: 600 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Severe Hypertriglyceridemia (Fredrickson Types IV and V)

Parameter Recommendation

Starting dose 600 mg orally twice daily

Titration Not usually required if tolerated

Usual maintenance dose 600 mg twice daily

Maximum dose 1200 mg/day (600 mg twice daily)

Key Clinical Notes:

• Administer 30 minutes before breakfast and dinner for optimal absorption

• Indicated primarily when fasting triglycerides >500 mg/dL with pancreatitis risk

• Assess triglyceride response at 8–12 weeks

• Discontinue if inadequate lipid response after 3 months of compliant therapy

• Ensure dietary and lifestyle modifications are concurrent

1. Type III Hyperlipoproteinemia (Familial Dysbetalipoproteinemia)

Parameter Recommendation

Starting dose 600 mg orally twice daily

Titration Not usually required

Usual maintenance dose 600 mg twice daily

Maximum dose 1200 mg/day

Key Clinical Notes:

• Confirm diagnosis with apolipoprotein E phenotyping or lipoprotein electrophoresis before initiation

• Characterized by elevated IDL (intermediate-density lipoprotein) and palmar xanthomas

• Excellent response expected in confirmed cases

1. Mixed Dyslipidemia (Elevated Triglycerides with Low HDL-C)

Parameter Recommendation

Starting dose 600 mg orally twice daily

Titration Not usually required

Usual maintenance dose 600 mg twice daily

Maximum dose 1200 mg/day

Key Clinical Notes:

• Consider when statins are contraindicated, not tolerated, or inadequate for triglyceride control

• Do NOT combine with statins routinely — high myopathy risk (see Major Drug Interactions)

• Evaluate complete lipid profile at 8–12 weeks

Secondary Indications — Adults Only (Off-label)

Not applicable — No widely accepted off-label indications in Indian practice.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Not applicable — Gemfibrozil is NOT approved for routine paediatric use in India due to insufficient safety and efficacy data.

Secondary Indications — Paediatric (Off-label)

Indication Age Dose Duration Notes

Severe Familial Hypertriglyceridemia ≥10 years 10–15 mg/kg/day in two divided doses (max: 1200 mg/day) Long-term OFF-LABEL — Specialist only (Paediatric Endocrinologist/Lipidologist). Limited evidence; based on extrapolation from adult data and international specialist practice

Safety Monitoring:

• LFTs every 3 months initially, then every 6 months

• Renal function (creatinine, eGFR) every 3–6 months

• Fasting lipid profile at baseline, 8 weeks, then every 3–6 months

• CK if muscle symptoms develop

• Monitor growth parameters

Statement: Gemfibrozil is NOT recommended in children <10 years. Use in children/adolescents is strictly off-label and requires specialist supervision with documented severe familial hypertriglyceridemia unresponsive to dietary measures.

Additional Notes:

• Gemfibrozil and its metabolites are primarily renally excreted

• Accumulation increases myopathy and rhabdomyolysis risk

Additional Notes:

• Discontinue if ALT/AST persistently >3× ULN

• Gemfibrozil undergoes hepatic metabolism

• Active hepatic disease or unexplained persistent transaminase elevation (>3× ULN)

• Severe renal impairment (eGFR <30 mL/min/1.73m²)

• Pre-existing gallbladder disease (cholelithiasis, cholecystitis, prior cholecystectomy for gallstones)

• Concurrent use with repaglinide — absolute contraindication (severe hypoglycaemia risk)

• Concurrent use with simvastatin or lovastatin — contraindicated due to high rhabdomyolysis risk

• Concurrent use with dasabuvir (HCV therapy)

• Known hypersensitivity to gemfibrozil or any excipient

• Concurrent use with selexipag

• History of myopathy or unexplained muscle pain

• Concurrent statin therapy (other than simvastatin/lovastatin) — use only if essential, with close CK monitoring

• Uncorrected hypothyroidism — correct thyroid function before initiation

• Elderly patients — increased myopathy risk; assess renal function before and during therapy

• Diabetes mellitus — may enhance hypoglycaemic effect of sulfonylureas; monitor blood glucose

• History of biliary tract disease or symptoms suggestive of gallstones

• Anticoagulant therapy — increased bleeding risk; requires INR adjustment

• Concurrent alcohol use — may worsen hypertriglyceridemia

Aspect Recommendation

Risk category Not recommended — Limited human data; animal studies inconclusive

Safety statement Avoid during pregnancy unless no safer alternative and benefit clearly outweighs risk

Preferred alternatives Dietary modification; Omega-3 fatty acids (under specialist guidance) for severe hypertriglyceridemia

When may be used Only in severe hypertriglyceridemia with imminent pancreatitis risk — specialist decision only

Monitoring If used: maternal LFTs, triglyceride levels, fetal growth monitoring

Aspect Recommendation

Compatibility Not recommended — Excretion in human milk unknown

Expected drug levels in milk Unknown

Preferred alternatives Dietary intervention; defer pharmacotherapy until breastfeeding completed

Infant monitoring If inadvertent exposure — monitor for GI disturbances, feeding difficulties, poor weight gain

Aspect Recommendation

Starting dose 600 mg once daily initially

Titration Slow; increase to twice daily only after assessing tolerability and renal function

Maximum dose 1200 mg/day if tolerated

Special considerations Assess renal function (eGFR) before initiation and periodically; higher myopathy risk especially with concurrent statin use; monitor CK if muscle weakness or pain develops; polypharmacy review essential for drug interactions

Interacting Drug Effect Recommendation

Simvastatin, Lovastatin Marked increase in statin levels via inhibition of glucuronidation and OATP1B1 → severe myopathy/rhabdomyolysis Contraindicated — do not co-prescribe

Repaglinide Inhibits CYP2C8 → markedly increased repaglinide levels → severe prolonged hypoglycaemia Contraindicated — do not co-prescribe

Warfarin, Acenocoumarol Displaces from protein binding; inhibits metabolism → enhanced anticoagulant effect Reduce anticoagulant dose by 30–50%; monitor INR every 2–3 days initially, then weekly until stable

Other statins (Atorvastatin, Rosuvastatin, Pravastatin) Increased myopathy risk (though lower than simvastatin/lovastatin) Avoid if possible; if essential, use lowest statin dose; fenofibrate preferred for statin combination

Colchicine Additive myotoxicity Avoid combination; if unavoidable, monitor CK closely

Dasabuvir Increased dasabuvir exposure Contraindicated

Selexipag Increased selexipag exposure Contraindicated

Enzalutamide Reduced gemfibrozil efficacy Avoid combination

Interacting Drug Effect Recommendation

Sulfonylureas (Glimepiride, Glipizide, Gliclazide) Enhanced hypoglycaemic effect Monitor blood glucose closely; may need sulfonylurea dose reduction

Pioglitazone Increased pioglitazone exposure via CYP2C8 inhibition; increased fluid retention and oedema risk Use with caution; consider pioglitazone dose reduction; monitor for oedema, heart failure symptoms

Bile acid sequestrants (Cholestyramine, Colesevelam) Reduced gemfibrozil absorption Administer gemfibrozil ≥2 hours before OR 4–6 hours after bile acid sequestrant

Ciclosporin Potential additive nephrotoxicity Monitor renal function closely

Montelukast Increased montelukast levels via CYP2C8 inhibition Usually clinically insignificant; monitor if adverse effects suspected

Ezetimibe Increased cholesterol excretion into bile → potential cholelithiasis risk Monitor for gallstone symptoms

• Dyspepsia, epigastric discomfort

• Abdominal pain

• Diarrhoea

• Nausea

• Fatigue

• Headache

• Elevated hepatic transaminases (ALT, AST) — usually transient

• Dizziness

• Eczema, rash

Adverse Effect Clinical Notes

Rhabdomyolysis Rare; significantly higher risk with statin combination or renal impairment; presents with severe muscle pain, weakness, dark urine; CK >10× ULN — STOP drug immediately; requires hospitalisation

Myopathy CK elevation 5–10× ULN with muscle symptoms; discontinue and monitor

Cholelithiasis (Gallstones) Fibrates increase biliary cholesterol saturation; monitor for biliary colic (RUQ pain), jaundice

Hepatotoxicity Persistent ALT/AST >3× ULN — discontinue; rarely cholestatic hepatitis

Anaemia, Leukopenia, Thrombocytopenia Rare haematological effects; monitor if unexplained bleeding, infections, fatigue

Pancreatitis Rare; paradoxical worsening possible; differentiate from underlying hypertriglyceridemia-induced pancreatitis

Hypersensitivity reactions Angioedema, urticaria, anaphylaxis (rare)

8–12 weeks after initiation Fasting lipid profile, LFTs

If on anticoagulants INR every 2–3 days initially, then weekly until stable

If muscle symptoms develop CK immediately; if >5× ULN with symptoms, discontinue

Long-term (stable therapy) LFTs every 6 months; lipid profile every 6–12 months; renal function annually; CBC annually; CK if symptomatic

Lopid Pfizer 300 mg capsule, 600 mg tablet

Normolip Micro Labs 300 mg capsule, 600 mg tablet

Gemcal Alkem 600 mg tablet

Lipigem Sun Pharma 300 mg capsule, 600 mg tablet

Fibrozil Cipla 600 mg tablet

Note: No fixed-dose combinations with statins are recommended due to high myopathy risk.

Note: Gemfibrozil is included in NLEM 2022 (600 mg tablet); NPPA price ceiling applicable for scheduled formulations. Prices vary by brand and region.

1. Administer 30 minutes before meals — food decreases rate but not extent of absorption; pre-meal dosing optimizes efficacy.

1. Do NOT routinely combine with statins — gemfibrozil inhibits statin glucuronidation causing markedly increased statin levels; if fibrate-statin combination is essential, use fenofibrate instead (different pharmacokinetic interaction profile).

1. Absolute contraindication with repaglinide — can cause severe, prolonged hypoglycaemia; use alternative diabetes therapy.

1. Screen for secondary causes — rule out hypothyroidism, nephrotic syndrome, uncontrolled diabetes, alcohol excess, and medications (e.g., isotretinoin, estrogens) before attributing hypertriglyceridemia to primary causes.

1. Gallstone risk — counsel patients regarding RUQ pain symptoms; fibrates increase biliary cholesterol saturation.

1. Discontinue if no response at 3 months — if triglycerides remain elevated despite adherence and lifestyle modification, reassess and consider alternative approaches.

gemfibrozil; fibrate; hypertriglyceridemia; type-III-dyslipidemia; pancreatitis-prevention; statin-alternative; myopathy-risk; rhabdomyolysis-caution; CYP2C8-inhibitor; NLEM-India; repaglinide-contraindicated

RxIndia v1.1 — 10 Jan 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia

• NLEM 2022

• API Textbook of Medicine

• ICMR Dyslipidemia Guidelines

• AIIMS Drug Formulary

• Goodman and Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• Lipid Association of India Guidelines

• Indian manufacturer product inserts (Pfizer, Cipla)